Preparation method and application of myrtenyl-1,3,4-oxadiazole formylhydrazine compounds

Abstract

The application discloses a preparation method and product of a myrtenyl-1,3,4-oxadiazole formylhydrazine compound and application of the compound, and synthesizes myrtenic acid by oxidizing myrtenal; myrtenyl hydrazine is generated by reacting the myrtenic acid with hydrazine hydrate; myrtenyl-1,3,4-oxadiazole methyl ester is generated by reacting the myrtenyl hydrazine with oxalyl chloride methyl ester; the myrtenyl-1,3,4-oxadiazole formylhydrazine compound is generated by reacting the myrtenyl-1,3,4-oxadiazole methyl ester with each substituted phenylhydrazine; the compound has a general formula I: wherein R is H, 4-F, 4-Cl, 4-Br, 4-I, 4-CH3, 2-CH3, 2-F, 3-F, 2-Cl, 3-Cl, 2-Br, 3-Br or 4-OCH3; the compound has good prevention effects on sclerotinia sclerotiorum, botryosphaeria dothidea and fusarium graminearum under an in-vitro condition, and can be used for preventing and treating fungal diseases of agricultural or forestry plants. The preparation method of the compound is simple, the yield is high, and the product is stable in property.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of pesticide synthesis, and particularly relates to a preparation method and application of a myrtenyl-1,3,4-oxadiazole formylhydrazine compound. BACKGROUND

[0002] The plant diseases and insect pests are one of important factors restricting the sustainable and healthy development of agricultural products and forest resources. As a special commodity for controlling biological hazards such as plant diseases and insect pests, the pesticide plays an important role in protecting the normal growth of the agricultural and forestry crops, improving the production of agriculture and promoting food safety.

[0003] At present, the long-term use of a single pesticide variety can also cause the plant pathogens, pests and weeds to have drug resistance, and therefore, it is crucial to develop a new pesticide variety with a targeted effect for effectively controlling the plant diseases.

[0004] So far, there is no report on the myrtenyl-1,3,4-oxadiazole formylhydrazine compound as an agricultural fungicide. SUMMARY

[0005] This section is intended to summarize some aspects of the embodiments of the present application and briefly introduce some preferred embodiments. Some simplifications or omissions may be made in this section and the abstract and title of the specification to avoid obscuring the purpose of this section, the abstract and the title, and such simplifications or omissions cannot be used to limit the scope of the present application.

[0006] In view of the above and / or problems existing in the prior art, the present application is proposed.

[0007] Therefore, the purpose of the present application is to overcome the deficiencies in the prior art and provide a myrtenyl-1,3,4-oxadiazole formylhydrazine compound.

[0008] To solve the above technical problems, the present application provides the following technical scheme: a myrtenyl-1,3,4-oxadiazole formylhydrazine compound, the structural formula of the myrtenyl-1,3,4-oxadiazole formylhydrazine compound is as follows:

[0009]

[0010] Among them, the R group is selected from one of 4-H, 4-F, 4-Cl, 4-Br, 4-I, 4-CH3, 2-CH3, 2-F, 3-F, 2-Cl, 3-Cl, 2-Br, 3-Br and 3-O-CH3.

[0011] Still another object of the present application is to overcome the deficiencies in the prior art and provide a preparation method of a class of myrtenyl-1,3,4-oxadiazole carbohydrazide compounds, comprising,

[0012] oxidizing myrtenal to synthesize myrtenic acid;

[0013] reacting myrtenic acid with hydrazine hydrate to generate myrtenyl hydrazide;

[0014] reacting myrtenyl hydrazide with oxalyl chloride methyl ester to generate myrtenyl-1,3,4-oxadiazole methyl ester;

[0015] reacting myrtenyl-1,3,4-oxadiazole methyl ester with substituted phenylhydrazine to synthesize myrtenyl-1,3,4-oxadiazole carbohydrazide compounds.

[0016] As a preferred scheme of the preparation method of the present application, wherein: the synthesis of myrtenic acid comprises,

[0017] dissolving myrtenal in acetonitrile, dissolving potassium dihydrogen phosphate in water, mixing the two in a single-neck flask under ice bath conditions, adding 30% hydrogen peroxide and PEG-400, dissolving sodium chlorite in water, slowly adding the sodium chlorite aqueous solution through a 50ml constant pressure funnel, reacting for 18h, detecting by TLC, adding sodium sulfite after the reaction is completed, removing acetonitrile by rotary evaporation, extracting with ethyl acetate, combining the organic layers, washing with saturated brine, drying with anhydrous sodium sulfate, and rotary evaporation to obtain the target compound myrtenic acid in an oily state;

[0018] wherein the molar ratio of myrtenal, potassium dihydrogen phosphate, hydrogen peroxide, PEG-400, sodium chlorite, and sodium sulfite is 1:0.25:1.1:0.14:1.3:0.07.

[0019] As a preferred scheme of the preparation method of the present application, wherein: the synthesis of myrtenyl hydrazide comprises,

[0020] dissolving myrtenic acid in anhydrous dichloromethane, then adding DMAP and EDCI, adding 85% hydrazine hydrate dropwise under ice bath, removing the ice bath after addition, detecting by TLC when the raw material is completely reacted, evaporating and concentrating to remove dichloromethane, extracting with ethyl acetate, combining the organic layers, washing with saturated brine, drying with anhydrous sodium sulfate, and rotary evaporation to obtain myrtenyl hydrazide crude product, and purifying by silica gel column chromatography with a 200-300 mesh silica gel column, and purifying with petroleum ether / ethyl acetate in a volume ratio of 10:1 to 3:1 to obtain the target compound myrtenyl hydrazide;

[0021] wherein the molar ratio of myrtenic acid, DMAP, EDCI, and hydrazine hydrate is 1:0.1:1.2:2.

[0022] As a preferred scheme of the preparation method, the synthesis of myrtenyl-1,3,4-oxadiazole methyl ester comprises,

[0023] The myrtenyl hydrazide is dissolved in phosphorus oxychloride, and oxalyl chloride methyl ester is added drop by drop under ice bath, after completion of addition, the reaction is carried out at 85 DEG C for 2 to 3 hours, the reaction solution is poured into ice water, stirring is carried out, ethyl acetate is added for extraction, the organic layers are combined, washed with saturated sodium bicarbonate, dried with anhydrous sodium sulfate, and concentrated by rotary evaporation to obtain the crude myrtenyl-1,3,4-oxadiazole methyl ester, which is purified by column chromatography with silica gel of 200-300 mesh, and purified by using petroleum ether / ethyl acetate with a volume ratio of 200:1 to 50:1, so as to obtain the target compound myrtenyl-1,3,4-oxadiazole methyl ester.

[0024] The molar ratio of the myrtenyl hydrazide and the oxalyl chloride methyl ester is 1:1.5.

[0025] As a preferred scheme of the preparation method, the synthesis of myrtenyl-1,3,4-oxadiazole methyl ester comprises,

[0026] The myrtenyl-1,3,4-oxadiazole methyl ester is dissolved in anhydrous DMF in a pressure-resistant tube, substituted phenylhydrazine is added, the temperature is raised to 100 DEG C, the reaction is carried out for 48 hours, then the reaction is stopped, desolventizing is carried out, ethyl acetate is added for extraction, the organic layers are combined, washed with saturated brine, dried with anhydrous sodium sulfate, and concentrated by rotary evaporation to obtain the substituted myrtenyl-1,3,4-oxadiazole methyl hydrazine, which is purified by column chromatography with silica gel of 200-300 mesh, and purified by using petroleum ether / ethyl acetate with a volume ratio of 200:1 to 20:1, so as to obtain the target compound substituted myrtenyl-1,3,4-oxadiazole methyl hydrazine.

[0027] The molar ratio of the myrtenyl-1,3,4-oxadiazole methyl ester and the substituted phenylhydrazine is 1:2.5.

[0028] As a preferred scheme of the preparation method, the substituted phenylhydrazine comprises phenylhydrazine, 4-fluorophenylhydrazine, 4-chlorophenylhydrazine, 4-bromophenylhydrazine, 4-iodophenylhydrazine, 4-methylphenylhydrazine, 2-methylphenylhydrazine, 2-fluorophenylhydrazine, 3-fluorophenylhydrazine, 2-chlorophenylhydrazine, 3-chlorophenylhydrazine, 2-bromophenylhydrazine, 3-bromophenylhydrazine, and 4-methoxyphenylhydrazine.

[0029] Another object of the present application is to overcome the defects in the prior art, and provide the application of the myrtenyl-1,3,4-oxadiazole methyl hydrazine compound in preventing and treating plant fungi in agriculture or forestry, wherein the plant fungi comprise botryosphaeria dothidea, sclerotinia sclerotiorum, botrytis cinerea, phytophthora infestans and phytophthora capsici.

[0030] The present application has the following beneficial effects:

[0031] (1) The compound described in the present application is a myrtenyl-1,3,4-oxadiazole formylhydrazine derivative, the molecular structure is novel, all are new compounds, the chemical structural characteristics are distinctive, the structural formula contains myrtenyl, oxadiazole group and formylhydrazine; the preparation method of the compound described in the present application is simple, the raw material is easy to obtain, and the reaction condition is mild and easy to control.

[0032] (2) The compound described in the present application is a medicine for preventing and treating plant fungi in the field of agriculture or forestry, and the medicine shows good effect on preventing and treating botryosphaeria dothidea, sclerotinia sclerotiorum, botrytis cinerea, phytophthora infestans and phytophthora capsici. BRIEF DESCRIPTION OF DRAWINGS

[0033] In order to more clearly illustrate the technical solutions of the embodiments of the present application, the drawings needed in the embodiment description will be briefly introduced. Obviously, the drawings in the following description are only some embodiments of the present application, and other drawings can be obtained by those skilled in the art without creative labor. Among them:

[0034] Figure 1 It is a preparation method schematic diagram of the myrtenyl-1,3,4-oxadiazole formylhydrazine compound in the embodiment of the present application.

[0035] Figure 2 It is an in vitro antifungal experiment graph of I-4 in different concentrations on botryosphaeria dothidea and sclerotinia sclerotiorum in the embodiment of the present application.

[0036] Figure 3 It is a protection and treatment experiment graph of I-4 at 100mg / L and 200mg / L on apple fruits infected by botryosphaeria dothidea in the embodiment of the present application. DETAILED DESCRIPTION

[0037] In order to make the above-mentioned purposes, features and advantages of the present application more obvious and easy to understand, the specific implementation manner of the present application will be described in detail in combination with the embodiment of the present application.

[0038] In the following description, many specific details are set forth in order to provide a thorough understanding of the present application, but the present application can also be implemented in other ways different from those described herein, and those skilled in the art can make similar generalizations without departing from the connotation of the present application, therefore the present application is not limited to the specific embodiments disclosed below.

[0039] Second, the "one embodiment" or "an embodiment" referred to herein can include a particular feature, structure, or characteristic. The various embodiments appearing at different places in this specification are not necessarily all cumulative with one another. Different aspects of the applications can be employed in each separate embodiment.

[0040] The preparation method of the myrtenyl-1,3,4-oxadiazole carbohydrazide compound of the application is shown in the following schematic diagram: Figure 1 , comprising the following steps:

[0041] (1) Myrtenal (purchased from Anjie Chemical City, CAS No. 18486-69-6) is oxidized to synthesize myrtenic acid;

[0042] (2) Myrtenic acid is reacted with hydrazine hydrate to generate myrtenyl hydrazide;

[0043] (3) Myrtenyl hydrazide is reacted with oxalyl chloride methyl ester to generate myrtenyl-1,3,4-oxadiazole methyl ester;

[0044] (4) Myrtenyl-1,3,4-oxadiazole methyl ester is reacted with each substituted phenylhydrazine to synthesize myrtenyl-1,3,4-oxadiazole carbohydrazide compound.

[0045] The specific steps are as follows:

[0046] (1) Preparation of myrtenic acid (II)

[0047] Myrtenal (500 mg, 3.3 mmol) is dissolved in 5 ml of acetonitrile, potassium dihydrogen phosphate (391 mg, 4.3 mmol) is dissolved in 3 ml of water, and the two are mixed in a 150 ml single-necked flask under ice bath conditions, 30% hydrogen peroxide (300 ul, 3.6 mmol) and PEG-400 (190 mg, 0.5 mmol) are added, sodium chlorite (391 mg, 4.3 mmol) is dissolved in 7 ml of water, and the sodium chlorite aqueous solution is slowly added dropwise through a 50 ml constant pressure funnel. After 18 h of reaction, TLC detection is performed, and after the reaction is completed, sodium sulfite (32 mg, 0.26 mmol) is added, rotary evaporation is performed to remove acetonitrile, ethyl acetate is added for extraction, the organic layers are combined, washed with saturated brine, dried over anhydrous sodium sulfate, and rotary evaporation is performed to obtain an oily substance myrtenic acid 450 mg;

[0048] 1H NMR (600 MHz, Chloroform-d) δ 6.99 (tt, J = 3.2, 1.5 Hz, 1H), 2.78 (td, J = 5.7, 1.6 Hz, 1H), 2.51 - 2.47 (m, 1H), 2.47 - 2.39 (m, 2H), 2.15 - 2.12 (m, 1H), 1.34 (s, 3H), 1.12 (d, J = 9.1 Hz, 1H), 0.79 (s, 3H). 13 C NMR (150 MHz, Chloroform-d) δ 171.37, 139.76, 139.61, 41.02, 40.35, 37.83, 32.51, 31.40, 25.98, 21.07. MS ESI m / z: calcd for C 10 H 14 O2Na[M+Na]+: 189.0891; found 189.0892.

[0049] (2) Preparation of myrtenyl hydrazide (III)

[0050] Myrtenic acid (500 mg, 3 mmol) was dissolved in 8 ml of anhydrous dichloromethane, then DMAP (36 mg, 0.3 mmol) and EDCI (689 mg, 4.2 mmol) were added, and 85% hydrazine hydrate (241 mg, 6 mmol) was added dropwise under ice bath. After the addition was completed, the ice bath was removed, and TLC detection showed that the reaction was complete. The dichloromethane was evaporated and concentrated, ethyl acetate was added for extraction, the organic layers were combined and washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated by rotary evaporation. The crude myrtenyl hydrazide was purified by column chromatography on 200-300 mesh silica gel, and eluted with petroleum ether / ethyl acetate (10:1 to 3:1, by volume) to obtain the target compound myrtenyl hydrazide 410 mg;

[0051] 1 H NMR (600 MHz, Chloroform-d) δ 6.40 (tt, J = 3.1, 1.5 Hz, 1H), 3.65 (s, 2H), 2.60 (td, J = 5.6, 1.6 Hz, 1H), 2.49 - 2.45 (m, 1H), 2.43 - 2.34 (m, 2H), 2.15 - 2.12 (m, 1H), 1.33 (s, 3H), 1.15 (d, J = 9.1 Hz, 1H), 0.82 (s, 3H). 13 C NMR (150 MHz, Chloroform-d) δ 168.40, 141.98, 130.23, 41.92, 40.54, 37.92, 31.95, 31.49, 26.04, 21.07. MS ESI m / z: calcd for C10 H 17 N2O[M+H]+: 181.1341; found 181.1339.

[0052] (3) Preparation of myrtenyl-1, 3, 4-oxadiazole methyl ester (IV)

[0053] Myrtenyl hydrazide (1 g, 3.7 mmol) was dissolved in 10 ml of phosphorus oxychloride, and oxalyl chloride methyl ester (690 mg, 5.6 mmol) was added dropwise under ice bath. After the addition was completed, the reaction was refluxed at 85°C for 2 to 3 hours. The reaction solution was poured into ice water and stirred. Ethyl acetate was added to extract, and the combined organic layer was washed with saturated sodium bicarbonate and dried over anhydrous sodium sulfate. The crude myrtenyl-1, 3, 4-oxadiazole methyl ester was obtained by rotary evaporation. The target compound myrtenyl-1, 3, 4-oxadiazole methyl ester was purified by column chromatography using 200-300 mesh silica gel and eluted with petroleum ether / ethyl acetate (200:1 to 50:1 by volume). The target compound was obtained in an amount of 700 mg.

[0054] 1 H NMR (600 MHz, Chloroform-d) δ 6.89 (tt, J = 3.3, 1.5 Hz, 1H), 4.04 (s, 3H), 3.12 - 3.09 (m, 1H), 2.61 - 2.58 (m, 1H), 2.58 - 2.56 (m, 1H), 2.52 (dt, J = 20.0, 3.1 Hz, 1H), 2.22 (ttd, J = 6.0, 2.9, 1.3 Hz, 1H), 1.39 (s, 3H), 1.27 (d, J = 9.3 Hz, 1H), 0.85 (s, 3H). 13 C NMR (150 MHz, Chloroform-d) δ 165.92, 155.78, 155.06, 134.47, 132.34, 53.76, 42.11, 40.29, 38.06, 32.62, 31.32, 25.83, 20.98. MS ESI m / z: calcd for C 13 H 16 N2O3Na[M+Na]+: 271.1059; found 271.1063.

[0055] (4) Preparation of each substituted myrtenyl-1, 3, 4-oxadiazole methyl hydrazine derivative (I)

[0056] Myrtenyl-1,3,4-oxadiazole methyl ester (500 mg, 2 mmol) was dissolved in 5 ml of anhydrous DMF in a 15 ml pressure tube, and phenylhydrazine (540 mg, 5 mmol) was added. The reaction was stopped after 48 hours of reaction at 100°C, and the solvent was removed. Ethyl acetate was added for extraction, and the organic layers were combined and washed with saturated brine. The mixture was dried over anhydrous sodium sulfate and concentrated by rotary evaporation. The crude product was purified by column chromatography on a 200-300 mesh silica gel column, and the target compound, myrtenyl-1,3,4-oxadiazole methyl hydrazine derivative (I-1), was obtained by purification with petroleum ether / ethyl acetate (200:1 to 20:1, by volume).

[0057] Example 1

[0058] Myrtenyl-1,3,4-oxadiazole methyl hydrazine derivative (I-1) was prepared.

[0059]

[0060] Myrtenyl-1,3,4-oxadiazole methyl ester (500 mg, 2 mmol) was dissolved in 5 ml of anhydrous DMF in a 15 ml pressure tube, and phenylhydrazine (540 mg, 5 mmol) was added. The reaction was stopped after 48 hours of reaction at 100°C, and the solvent was removed. Ethyl acetate was added for extraction, and the organic layers were combined and washed with saturated brine. The mixture was dried over anhydrous sodium sulfate and concentrated by rotary evaporation. The crude product was purified by column chromatography on a 200-300 mesh silica gel column, and the target compound, myrtenyl-1,3,4-oxadiazole methyl hydrazine derivative (I-1), was obtained by purification with petroleum ether / ethyl acetate (200:1 to 20:1, by volume).

[0061] White solid;Yield:30.5%; 1 H NMR (600 MHz, Chloroform-d) δ 9.11 (s, 1H), 7.25-7.21 (m, 2H), 6.94 (tt, J = 7.4, 1.1 Hz, 1H), 6.90 (d, J = 1.2 Hz, 1H), 6.88-6.87 (m, 2H), 3.08 (td, J = 5.6, 1.5 Hz, 1H), 2.60-2.57 (m, 1H), 2.57-2.48 (m, 2H), 2.24-2.22 (m, 1H), 1.39 (s, 3H), 1.26 (d, J = 9.3 Hz, 1H), 0.85 (s, 3H). 13CNMR (151 MHz, Chloroform-d) δ 166.05, 156.70, 153.80, 146.71, 134.47, 132.03, 129.29, 121.89, 113.84, 42.07, 40.20, 37.99, 32.54, 31.23, 25.77, 20.91. MS ESI m / z: calcd for C 18 H 21 N4O2[M+H]+: 325.1665; found 325.1660.

[0062] Example 2

[0063] Example 2

[0064]

[0065] The myrtenyl-1,3,4-oxadiazole methyl hydrazine derivative (I-2) was prepared by dissolving the myrtenyl-1,3,4-oxadiazole methyl ester (500 mg, 2 mmol) in 15 ml of a pressure-resistant tube with 5 ml of anhydrous DMF, adding 4-fluorobenzene hydrazine (630 mg, 5 mmol), and stopping the reaction after 48 hours of reaction at 100°C. The reaction solution was removed, extracted with ethyl acetate, and the organic layers were combined and washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated by rotary evaporation to obtain a crude product. The crude product was purified by column chromatography on a 200-300 mesh silica gel column, and purified with petroleum ether / ethyl acetate (200:1 to 20:1 by volume) to obtain the target compound myrtenyl-1,3,4-oxadiazole methyl hydrazine derivative (I-2). Light yellow solid; yield: 34.5%.

[0066] Yellow solid; Yield: 35.0%; 1 H NMR (600 MHz, Chloroform-d) δ 9.26 (s, 1H), 6.94 - 6.90 (m, 2H), 6.86 (ddt, J = 9.0, 6.7, 3.1 Hz, 3H), 3.06 (td, J = 5.6, 1.5 Hz, 1H), 2.60 - 2.57 (m, 1H), 2.52 (tt, J = 20.1, 3.3 Hz, 2H), 2.23 - 2.20 (m, 1H), 1.38 (s, 3H), 1.25 (d, J = 9.3 Hz, 1H), 0.84 (s, 3H). 13C NMR (151 MHz, Chloroform-d) δ 166.18, 158.42 (d, J = 238.5 Hz), 156.76, 154.02, 142.97 (d, J = 3.0 Hz), 134.74, 132.11, 115.98 (d, J = 24.0 Hz), 115.64 (d, J = 9.0 Hz), 42.19, 40.30, 38.10, 32.66, 31.33, 25.87, 21.02. MS ESI m / z: calcd for C 18 H 20 N4O2F [M+H]+: 343.1570; found 343.1573.

[0067] Example 3

[0068] The myrtenyl-1,3,4-oxadiazole carbohydrazide derivative (I-3) was prepared:

[0069]

[0070] The myrtenyl-1,3,4-oxadiazole carbohydrazide derivative (I-3) was prepared:

[0071] Light Yellow solid;Yield:34.5%; 1 H NMR (600 MHz, Chloroform-d) δ 9.27 (s, 1H), 7.18 - 7.15 (m, 2H), 6.87 (tt, J = 3.2, 1.4 Hz, 1H), 6.83 - 6.79 (m, 2H), 3.05 (td, J = 5.6, 1.5 Hz, 1H), 2.60 - 2.57 (m, 1H), 2.56 - 2.48 (m, 2H), 2.23 - 2.20 (m, 1H), 1.38 (s, 3H), 1.25 (d, J = 9.3 Hz, 1H), 0.84 (s, 3H). 13C NMR (151 MHz, Chloroform-d) δ 166.10, 156.58, 153.90, 145.40, 134.73, 131.96, 129.20, 126.69, 115.09, 42.07, 40.18, 37.99, 32.55, 31.21, 25.75, 20.90. MS ESI m / z: calcd for C 18 H 19 N4O2NaCl[M+Na]+: 381.1094; found 381.1089.

[0072] Example 4

[0073] The myrtenyl-1,3,4-oxadiazole carbohydrazide derivative (I-4) was prepared:

[0074]

[0075] The myrtenyl-1,3,4-oxadiazole carbohydrazide derivative (I-4) was prepared:

[0076] White solid; Yield: 39.5%; 1 H NMR (600 MHz, Chloroform-d) δ 9.28 (s, 1H), 7.33 - 7.29 (m, 2H), 6.87 (tt, J = 3.4, 1.5 Hz, 1H), 6.78 - 6.74 (m, 2H), 3.05 (td, J = 5.6, 1.5 Hz, 1H), 2.58 (dt, J = 8.3, 2.7 Hz, 1H), 2.57 - 2.48 (m, 2H), 2.23 - 2.20 (m, 1H), 1.38 (s, 3H), 1.25 (d, J = 9.3 Hz, 1H), 0.84 (s, 3H). 13C NMR (151 MHz, Chloroform-d) δ 166.21, 156.69, 154.00, 146.03, 134.85, 132.21, 132.07, 115.58, 114.06, 42.18, 40.30, 38.10, 32.67, 31.33, 25.87, 21.03. MS ESI m / z: calcd for C 18 H 19 N4O2NaBr[M+Na]+: 425.0589; found 425.0585.

[0077] Example 5

[0078] The myrtenyl-1,3,4-oxadiazole carbohydrazide derivative (I-5) was prepared:

[0079]

[0080] The myrtenyl-1,3,4-oxadiazole carbohydrazide derivative (I-5) was prepared: The myrtenyl-1,3,4-oxadiazole methyl ester (500 mg, 2 mmol) was dissolved in 15 ml of a pressure tube with 5 ml of anhydrous DMF, 4-iodophenylhydrazine (1170 mg, 5 mmol) was added, and the reaction was stopped after being heated to 100 °C for 48 h, desolved, extracted with ethyl acetate, the organic layers were combined, washed with saturated brine, dried with anhydrous sodium sulfate, and concentrated by rotary evaporation to obtain a crude product, which was separated and purified by column chromatography on 200-300 mesh silica gel, purified with petroleum ether / ethyl acetate in a volume ratio of 200:1 to 20:1, to obtain the target compound myrtenyl-1,3,4-oxadiazole carbohydrazide derivative (I-5). Yellow oily substance; Yield: 29.5%

[0081] Yellow oily substance; Yield: 29.5%; 1 H NMR (600 MHz, Chloroform-d) δ 9.00 (s, 1H), 7.52 (d, J = 8.3 Hz, 2H), 6.90-6.88 (m, 1H), 6.67 (d, J = 8.5 Hz, 2H), 3.07 (td, J = 5.6, 1.5 Hz, 1H), 2.60 (dt, J = 8.5, 2.8 Hz, 1H), 2.58-2.49 (m, 2H), 2.23 (qd, J = 5.7, 4.7, 2.4 Hz, 1H), 1.39 (s, 3H), 1.27 (d, J = 9.3 Hz, 1H), 0.85 (s, 3H). 13C NMR (151 MHz, CDC13) δ 166.30, 156.67, 153.98, 146.76, 138.18, 134.86, 132.14, 116.00, 84.03, 42.21, 40.32, 38.12, 32.69, 31.35, 25.89, 21.04. MS ESI m / z: calcd for C 18 H 19 N4O2NaI[M+Na]+: 473.0450; found 473.0441.

[0082] Example 6

[0083] The myrtenyl-1,3,4-oxadiazole carbohydrazide derivative (I-6) was prepared:

[0084]

[0085] The myrtenyl-1,3,4-oxadiazole carbohydrazide derivative (I-6) was prepared:

[0086] White solid;Yield:32.5%; 1 H NMR (600 MHz, Chloroform-d) δ 9.11 (s, 1H), 7.04 (s, 1H), 7.02 (s, 1H), 6.87 (tt, J = 3.3, 1.5 Hz, 1H), 6.81 (d, J = 1.9 Hz, 1H), 6.80 (d, J = 2.0 Hz, 1H), 3.08 (td, J = 5.6, 1.5 Hz, 1H), 2.60 - 2.57 (m, 1H), 2.57 - 2.48 (m, 2H), 2.26 (s, 3H), 2.22 (m, 1H), 1.39 (s, 3H), 1.26 (d, J = 9.3 Hz, 1H), 0.85 (s, 3H). 13C NMR(151MHz,Chloroform-d)δ166.12,156.88,153.86,144.46,134.49,132.18,13 1.50,129.89,114.29,42.18,40.32,38.10,32.63,31.33,25.87,21.01,20.70.MS ESI m / z:calcd forC 19 H 22 N4O2Na[M+Na]+:361.1640; found361.1628.

[0087] Example 7

[0088] The myrtyl-1,3,4-oxadiazole carbamoylhydrazine derivative (I-7) was prepared:

[0089]

[0090] Myrtyl-1,3,4-oxadiazole methyl ester (500 mg, 2 mmol) was dissolved in 5 mL of anhydrous DMF in a 15 mL pressure-resistant tube. 2-Methylphenylhydrazine (610 mg, 5 mmol) was added, and the reaction was carried out at 100 °C for 48 hours. The reaction was then stopped, the solvent was removed, and the mixture was extracted with ethyl acetate. The combined organic layers were washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated by rotation to obtain the crude product. The crude product was purified by silica gel column chromatography (200-300 mesh) at a petroleum ether / ethyl acetate ratio of 200:1 to 20:1 (v / v) to give the target compound, myrtyl-1,3,4-oxadiazole carbamoylhydrazine derivative (Ⅰ-7). White solid; yield: 42.5%

[0091] White solid; Yield: 42.5%; 1 H NMR(600MHz,Chloroform-d)δ9.04(s,1H),7.11(s,1H),7.10(s,1H),6.89(ddd,J=7.3,4.6,1.1Hz,3H),3.08(td,J=5.6,1.5Hz, 1H),2.60–2.57(m,1H),2.53(tt,J=20.0,3.1Hz,2H),2.29(s,3H),2.22(m,1H),1.39(s,3H),1.27(d,J=9.3Hz,1H),0.86(s,3H). 13C NMR (151 MHz, Chloroform-d) δ 166.18, 156.85, 153.69, 144.61, 134.58, 132.18, 130.83, 127.14, 123.74, 121.87, 112.67, 42.20, 40.33, 38.11, 32.66, 31.35, 25.89, 21.04, 17.17. MS ESI m / z: calcd for C 19 H 22 N4O2Na[M+Na]+: 361.1640; found 361.1628.

[0092] Example 8

[0093] The myrtenyl-1,3,4-oxadiazole carbohydrazide derivative (I-8) was prepared:

[0094]

[0095] The myrtenyl-1,3,4-oxadiazole carbohydrazide derivative (I-8) was prepared: The myrtenyl-1,3,4-oxadiazole carboxylate (500 mg, 2 mmol) was dissolved in 15 ml of a pressure tube with 5 ml of anhydrous DMF, 2-fluorobenzenehydrazine (630 mg, 5 mmol) was added, and the reaction was stopped after being heated to 100 °C for 48 h, desolved, extracted with ethyl acetate, the organic layers were combined, washed with saturated brine, dried with anhydrous sodium sulfate, and concentrated by rotary evaporation to obtain a crude product, which was purified by column chromatography on a 200-300 mesh silica gel column, and purified with petroleum ether / ethyl acetate (volume ratio 200:1-20:1) to obtain the target compound myrtenyl-1,3,4-oxadiazole carbohydrazide derivative (I-8). Yellow oily substance; Yield: 22.5%

[0096] Yellow oily substance; Yield: 22.5%; 1 H NMR (600 MHz, Chloroform-d) δ 9.13 (s, 1H), 7.04 (ddd, J = 11.3, 8.0, 1.3 Hz, 1H), 7.00 (dd, J = 7.6, 1.4 Hz, 1H), 6.97 (td, J = 8.2, 1.9 Hz, 1H), 6.89 (tq, J = 5.5, 2.2 Hz, 2H), 3.07 (td, J = 5.6, 1.6 Hz, 1H), 2.59 (dt, J = 8.5, 2.8 Hz, 1H), 2.53 (tt, J = 20.1, 3.3 Hz, 2H), 2.22 (dtd, J = 6.1, 3.2, 1.5 Hz, 1H), 1.39 (s, 3H), 1.26 (d, J = 9.3 Hz, 1H), 0.84 (s, 3H). 13C NMR (151 MHz, Chloroform-d) δ 166.23, 156.71, 153.91, 151.68 (d, J = 240 Hz), 135.00 (d, J = 10.5 Hz), 134.70, 132.16, 124.68 (d, J = 4.5 Hz), 122.08 (d, J = 7.5 Hz), 115.52 (d, J = 18 Hz), 115.03 (d, J = 1.5 Hz), 42.18, 40.31, 38.10, 32.66, 31.33, 25.87, 21.02. MS ESI m / z: calcd for C 18 H 19 N4O2NaF[M+Na]+:365.1390; found 365.1385.

[0097] Example 9

[0098] The myrtenyl-1,3,4-oxadiazole carbohydrazide derivative (I-9) was prepared:

[0099]

[0100] The myrtenyl-1,3,4-oxadiazole carbohydrazide derivative (I-9) was prepared:

[0101] White solid;Yield:32.5%; 1 H NMR (600 MHz, Chloroform-d) δ 9.16 (s, 1H), 7.17 (td, J = 8.2, 6.4 Hz, 1H), 6.88 (tt, J = 3.4, 1.5 Hz, 1H), 6.66 (dd, J = 7.6, 2.1 Hz, 1H), 6.61 (td, J = 9.1, 2.3 Hz, 2H), 3.07 (td, J = 5.6, 1.5 Hz, 1H), 2.61 - 2.57 (m, 1H), 2.57 - 2.48 (m, 2H), 2.22 (dp, J = 8.7, 2.5 Hz, 1H), 1.39 (s, 3H), 1.26 (d, J = 9.3 Hz, 1H), 0.85 (s, 3H). 13C NMR(151MHz,Chloroform-d)δ166.23,163.81(d,J=214.5Hz),156.70,154.04,148.84(d,J=10.5Hz),134.81,132.10,130.67(d, J=9.0Hz),109.37(d,J=3.0Hz),108.45(d,J=21.0Hz),101.22(d,J=25.5Hz),42.17,40.30,38.09,32.65,31.32,25.85,21.00.MS ESIm / z:calcd for C 18 H 19 N4O2NaF[M+Na]+:365.1390; found 365.1386.

[0102] Example 10

[0103] The myrtyl-1,3,4-oxadiazole carbamoylhydrazine derivative (I-10) was prepared:

[0104]

[0105] Myrtyl-1,3,4-oxadiazole methyl ester (500 mg, 2 mmol) was dissolved in 5 mL of anhydrous DMF in a 15 mL pressure-resistant tube. 2-Chlorophenylhydrazine (710 mg, 5 mmol) was added, and the reaction was carried out at 100 °C for 48 hours. The reaction was then stopped, the solvent was removed, and the mixture was extracted with ethyl acetate. The combined organic layers were washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated by rotation to obtain the crude product. The crude product was purified by silica gel column chromatography (200-300 mesh) at a petroleum ether / ethyl acetate ratio of 200:1 to 20:1 (v / v) to give the target compound, myrtyl-1,3,4-oxadiazole carbamoylhydrazine derivative (Ⅰ-10). White solid; yield: 29.5%.

[0106] White solid; Yield: 32.5%; 1 H NMR(600MHz,Chloroform-d)δ9.38(s,1H),7.28(dd,J=8.0,1.4Hz,1H),7.12(ddd,J=8.4,7.4,1.4Hz,1H),6.93(dd,J=8.2,1.5Hz,1H),6.88–6.83(m,2 H),6.68(s,1H),3.05(td,J=5.6,1.5Hz,1H),2.59–2.56(m,1H),2.56–2.47 (m,2H),2.22–2.19(m,1H),1.38(s,3H),1.24(d,J=9.3Hz,1H),0.83(s,3H).13 C NMR (151 MHz, Chloroform-d) δ 166.16, 156.72, 153.81, 142.87, 134.71, 132.09, 129.66, 127.83, 122.04, 119.79, 113.86, 42.13, 40.28, 38.06, 32.63, 31.30, 25.84, 20.99. MS ESIm / z: calcd for C 18 H 19 N4O2NaCl [M+Na]+: 381.1094; found 381.1080.

[0107] Example 11

[0108] The myrtenyl-1,3,4-oxadiazole carbohydrazide derivative (I-11) was prepared:

[0109]

[0110] The myrtenyl-1,3,4-oxadiazole carbohydrazide derivative (I-11) was prepared:

[0111] Yellow oily substance;Yield:31.2%; 1 H NMR (600 MHz, Chloroform-d) δ 9.23 (s, 1H), 7.13 (t, J = 8.3 Hz, 1H), 6.89 (ddd, J = 5.0, 2.8, 1.5 Hz, 3H), 6.76 (ddd, J = 8.2, 2.2, 1.0 Hz, 1H), 3.06 (td, J = 5.6, 1.5 Hz, 1H), 2.59 (dt, J = 7.9, 2.6 Hz, 1H), 2.56 - 2.48 (m, 2H), 2.23 - 2.20 (m, 1H), 1.38 (s, 3H), 1.26 (d, J = 9.3 Hz, 1H), 0.84 (s, 3H). 13C NMR (151 MHz, Chloroform-d) δ 166.26, 156.68, 154.04, 148.20, 135.26, 134.84, 132.12, 130.45, 121.90, 113.91, 112.07, 42.19, 40.31, 38.11, 32.67, 31.34, 25.87, 21.03. MS ESI m / z: calcd for C 18 H 19 N4O2NaCl[M+Na]+: 381.1094; found 381.1080.

[0112] Example 12

[0113] Example 12

[0114]

[0115] Example 12

[0116] White oily substance;Yield:33.7%; 1 H NMR (600 MHz, Chloroform-d) δ 8.98 (s, 1H), 7.48 (dd, J = 8.0, 1.4 Hz, 1H), 7.20 (td, J = 7.8, 1.4 Hz, 1H), 6.93 (dd, J = 8.1, 1.5 Hz, 1H), 6.90 (tt, J = 3.4, 1.4 Hz, 1H), 6.82 (td, J = 7.6, 1.5 Hz, 1H), 6.57 (s, 1H), 3.09 (td, J = 5.6, 1.5 Hz, 1H), 2.61 - 2.57 (m, 2H), 2.52 (dt, J = 20.0, 3.1 Hz, 1H), 2.24 - 2.21 (m, 1H), 1.39 (s, 3H), 1.27 (d, J = 9.3 Hz, 1H), 0.86 (s, 3H). 13CNMR (151 MHz, Chloroform-d) δ 166.31, 156.68, 153.75, 143.80, 134.77, 132.97, 132.19, 128.61, 122.74, 113.99, 109.40, 42.21, 40.34, 38.13, 32.69, 31.36, 25.89, 21.05. MS ESI m / z: calcd for C 18 H 19 N4O2NaBr[M+Na]+: 425.0589; found 425.0578.

[0117] Example 13

[0118] Example 13

[0119]

[0120] The myrtenyl-1,3,4-oxadiazole methyl hydrazine derivative (I-13) was prepared by dissolving the myrtenyl-1,3,4-oxadiazole methyl ester (500 mg, 2 mmol) in 15 ml of a pressure tube with 5 ml of anhydrous DMF, adding 3-bromophenylhydrazine (935 mg, 5 mmol), and stopping the reaction after 48 hours of reaction at 100°C, dissolving, adding ethyl acetate for extraction, combining the organic layers, washing with saturated brine, drying with anhydrous sodium sulfate, and rotary concentrating to obtain a crude product, which was purified by column chromatography with 200-300 mesh silica gel, and purified with petroleum ether / ethyl acetate in a volume ratio of 200:1 to 20:1 to obtain the target compound myrtenyl-1,3,4-oxadiazole methyl hydrazine derivative (I-13). White oily substance; yield: 28.7%

[0121] White oily substance; yield: 28.7%; 1 H NMR (600 MHz, Chloroform-d) δ 9.00 (s, 1H), 7.10 (t, J = 8.2 Hz, 1H), 7.06 (dt, J = 7.2, 1.6 Hz, 2H), 6.90 (tt, J = 3.3, 1.4 Hz, 1H), 6.83–6.80 (m, 1H), 6.33 (s, 1H), 3.08 (td, J = 5.6, 1.5 Hz, 1H), 2.60 (dt, J = 8.2, 2.7 Hz, 1H), 2.57 (t, J = 4.1 Hz, 1H), 2.52 (dt, J = 20.1, 3.1 Hz, 1H), 2.24–2.21 (m, 1H), 1.39 (s, 3H), 1.27 (d, J = 9.3 Hz, 1H), 0.86 (s, 3H). 13C NMR (151 MHz, Chloroform-d) δ 166.33, 156.63, 154.00, 148.28, 134.84, 132.17, 130.78, 124.96, 123.37, 116.78, 112.56, 42.22, 40.33, 38.14, 32.69, 31.36, 25.90, 21.05. MS ESI m / z: calcd for C 18 H 20 N4O2Br[M+H]+: 403.0770; found 403.0764.

[0122] Example 14

[0123] The myrtenyl-1,3,4-oxadiazole carbohydrazide derivative (I-14) was prepared:

[0124]

[0125] The myrtenyl-1,3,4-oxadiazole carbohydrazide derivative (I-14) was prepared:

[0126] White solid;Yield:28.7%; 1 H NMR (600 MHz, Chloroform-d) δ 8.82 (s, 1H), 6.90 (d, J = 2.2 Hz, 1H), 6.90 - 6.88 (m, 2H), 6.83 (d, J = 2.3 Hz, 1H), 6.82 (d, J = 2.3 Hz, 1H), 3.76 (s, 3H), 3.09 (td, J = 5.6, 1.6 Hz, 1H), 2.61 - 2.58 (m, 1H), 2.55 (dt, J = 20.9, 3.2 Hz, 2H), 2.24 - 2.21 (m, 1H), 1.39 (s, 3H), 1.28 (s, 1H), 0.85 (s, 3H). 13C NMR (151 MHz, Chloroform-d) δ 166.21, 156.85, 155.47, 153.88, 140.34, 134.54, 132.22, 116.31, 114.83, 55.76, 42.23, 40.35, 38.13, 32.67, 31.36, 25.90, 21.04. MS ESI m / z: calcd for C 19 H 22 N4O2Na[M+Na]+: 377.1590; found 377.1582.

[0127] Example 15

[0128] Bactericidal activity (in vitro) experiments:

[0129] All test strains in this experiment were purchased from China Agricultural Microbial Culture Collection Center (ACCC) and China Forestry Culture Collection Center (CFCC), which were Gibberella zeae (ACCC 31060), Rhizoctonia solani (ACCC 38870), Phytophthora capsici (ACCC 36279), Botrytis cinerea (ACCC 36027), Sclerotinia sclerotiorum (ACCC 30096), Colletotrichum capsici (ACCC 37623) and Phytophthora infestans (ACCC 36278). MYA-1113 TM The medium used was potato agar glucose medium (PDA for short). The PDA medium formula: potato (peeled) 200 g, glucose 20 g, agar 15 g, distilled water 1000 mL, preparation method: wash and peel the potatoes, weigh 200 g and cut into small pieces, cook until soft (boil for 20-30 minutes, which can be poked by a glass rod), filter in a beaker with eight layers of gauze, add 15-20 g of agar according to the experimental needs, add 20 g of glucose, stir evenly, dissolve thoroughly, cool slightly, make up to 1000 mL with water, sterilize at 121°C for 15 minutes after dispensing, and cool down for standby.

[0130] Experimental method: growth rate method.

[0131] (1) First, 7 kinds of plant fungi were cultured on PDA plates at 25°C for 3-6 days for standby;

[0132] (2) The PDA medium was heated and dissolved, cooled to 45-50°C, and 50 mg / L of the test compound was added to prepare a medium containing 50 mg / L of the test compound, and was cooled in a culture dish, bixafen was used as a positive control;

[0133] (3) With sterile operation procedure, punch a round mycelium cake (0.50 cm in diameter) at the edge of mycelium of each strain cultured for 6 days (with the same growth condition as possible) with puncher, pick it to the center of the plate containing drug with inoculation needle, then place the culture dish upside down in the incubator (28℃) for culture;

[0134] (4) Observe and determine the growth condition of mycelium at different time after treatment, measure the diameter with cross method and process data, and calculate the inhibition rate;

[0135] Inhibition rate (%) = (diameter of control mycelium - diameter of treated mycelium) / (diameter of control mycelium - 0.5) x 100;

[0136] Each treatment is repeated for 3 times.

[0137] Table 1 Inhibition activity test results of rhodomyrtexenyl-1,3,4-oxadiazole carbohydrazide compounds on seven agricultural pathogenic fungi

[0138]

[0139]

[0140] Note: Three repetitions are set for each treatment in the test, and the data in the table is the average value of three repetitions.

[0141] Table 2 EC values (mg / L) of some compounds 50

[0142]

[0143] The results of bactericidal activity determination of experimental groups I-1 to I-14 and the control fungicide carbendazim are shown in Table 1.

[0144] As shown in Table 1 and Table 2, at the concentration of 25 mg / L, compounds I-1 to I-14 show different degrees of inhibition activity on six plant fungi, some compounds show better inhibition activity on Sclerotinia sclerotiorum, Botryosphaeria dothidea, Gibberella zeae and Valsa mali, and show moderate inhibition activity on Phytophthora infestans, Pythium capsici and Botrytis cinerea. The inhibition rate of some compounds on Phytophthora infestans is higher than that of the control fungicide carbendazim. It is indicated that the inhibition activity of these compounds on the fungus is equivalent to that of the positive control drug carbendazim, and has the potential to develop antifungal agents.

[0145] As shown in Table 1 and Table 2, at the concentration of 25 mg / L, compounds I-1 to I-14 show different degrees of inhibition activity on six plant fungi, some compounds show better inhibition activity on Sclerotinia sclerotiorum, Botryosphaeria dothidea, Gibberella zeae and Valsa mali, and show moderate inhibition activity on Phytophthora infestans, Pythium capsici and Botrytis cinerea. The inhibition rate of some compounds on Phytophthora infestans is higher than that of the control fungicide carbendazim. It is indicated that the inhibition activity of these compounds on the fungus is equivalent to that of the positive control drug carbendazim, and has the potential to develop antifungal agents.

[0146] Figure 2 It can be seen that, at different concentrations, the inhibition rate of compound I-4 on Botryosphaeria dothidea and Gibberella zeae has a gradient change, and conforms to EC 50 ​The calculation results show that the compound has good inhibitory effect on the two kinds of pathogenic bacteria.

[0147] Example 17

[0148] Bactericidal activity test:

[0149] Uniform and smooth apples of uniform texture and size were purchased from the market, washed with sterilized water, then washed with 75% ethanol, and dried at room temperature. An appropriate amount of compound I-4 was weighed, and dissolved in 0.2% Tween-80 water solution to prepare two concentrations of 200 mg / L and 100 mg / L.

[0150] Protection activity test method: Each apple surface was sprayed (5 mL of spray amount, one concentration), and the spray was uniform, and then naturally air-dried. After the fruit surface was free of liquid, the skin was pierced with an inoculation needle, and grapevine cavity fungus cakes (0.5 cm in diameter) were inoculated, three cakes per fruit. The positive control was boscalid. The fruits were cultured under indoor conditions (25±2°C and 95% relative humidity) for 6 days, the lesion diameters were measured, and the inhibition rate was calculated. The inhibition rate calculation formula (%): (blank control lesion diameter-test compound lesion diameter) / (blank control lesion diameter-0.5) x 100%.

[0151] Protection activity test method: Each apple surface was sprayed (5 mL of spray amount, one concentration), and the spray was uniform, and then naturally air-dried. After the fruit surface was free of liquid, the skin was pierced with an inoculation needle, and grapevine cavity fungus cakes (0.5 cm in diameter) were inoculated, three cakes per fruit. The positive control was boscalid. The fruits were cultured under indoor conditions (25±2°C and 95% relative humidity) for 6 days, the lesion diameters were measured, and the inhibition rate was calculated. The inhibition rate calculation formula (%): (blank control lesion diameter-test compound lesion diameter) / (blank control lesion diameter-0.5) x 100%.

[0152] Treatment activity test method: The skin was pierced with an inoculation needle, and grapevine cavity fungus cakes (0.5 cm in diameter) were inoculated, three cakes per fruit. Then each apple surface was sprayed (5 mL of spray amount, one concentration, and the positive control was carbendazim), and the spray was uniform, and then naturally air-dried. After the fruit surface was free of liquid, the fruits were cultured under indoor conditions (25±2°C and 95% relative humidity) for 6 days, the lesion diameters were measured, and the inhibition rate was calculated. The inhibition rate calculation formula (%): (blank control lesion diameter-test compound lesion diameter) / (blank control lesion diameter-0.5) x 100%.

[0153] Table 3 Compound I-4 in vivo biological activity on Botryosphaeria dothidea (apple fruit in vivo)

[0154]

[0155] As can be seen in Table 3 and Figure 3 Table 4, at a concentration of 200 mg / L, the protective activity and therapeutic activity of compound I-4 were 92.1% and 85.0%, respectively, both of which were superior to 74.3% and 63.5% of the positive control carbendazim. Further reducing the concentration to 100 mg / L, the protective activity and therapeutic activity of compound I-4 were 77.9% and 75.2%, respectively, which were also superior to 33.4% and 39.9% of the positive control carbendazim. The results showed that compound I-4 had potential value for developing antifungal pesticides.

[0156] It should be noted that the above examples are only used to illustrate the technical solutions of the present application and not to limit the present application. Although the present application has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solutions of the present application can be modified or replaced by equivalents without departing from the spirit and scope of the present application, which should be covered in the scope of the present application.

Claims

1. Compounds of the myrtenyl-1,3,4-oxadiazolecarbohydrazide class, characterized in that: The structural formula of the myrtenyl-1,3,4-oxadiazole formyl hydrazine compound is as follows: The R group is selected from one of 4-H, 4-F, 4-Cl, 4-Br, 4-I, 4-CH3, 2-CH3, 2-F, 3-F, 2-Cl, 3-Cl, 2-Br, 3-Br and 3-O-CH3.

2. A process for the preparation of the myrtenyl-1,3,4-oxadiazolecarbohydrazide compounds according to claim 1, characterized by: It comprises, Myrtenal is oxidized to synthesize myrtenic acid; Myrtenic acid is reacted with hydrazine hydrate to generate myrtenyl hydrazine; Myrtenyl hydrazine is reacted with oxalyl chloride methyl ester to generate myrtenyl-1,3,4-oxadiazole methyl ester; Myrtenyl-1,3,4-oxadiazole methyl ester is reacted with substituted phenylhydrazine to synthesize myrtenyl-1,3,4-oxadiazole formyl hydrazine compound; The preparation route is as follows: The R group is selected from one of 4-H, 4-F, 4-Cl, 4-Br, 4-I, 4-CH3, 2-CH3, 2-F, 3-F, 2-Cl, 3-Cl, 2-Br, 3-Br and 3-O-CH3.

3. The production method according to claim 2, characterized by: The synthesis of myrtenic acid comprises, Myrtenal is dissolved in acetonitrile, and potassium dihydrogen phosphate is dissolved in water. Under ice bath condition, the two are mixed in a single-neck flask, 30% hydrogen peroxide and PEG-400 are added, sodium chlorite is dissolved in water, and the sodium chlorite aqueous solution is slowly added dropwise through a 50ml constant-pressure funnel. After 18h of reaction, TLC detection is performed, and after the reaction is completed, sodium sulfite is added, rotary evaporation is performed to remove acetonitrile, ethyl acetate is added for extraction, the organic layers are combined, saturated brine is used for washing, anhydrous sodium sulfate is used for drying, and rotary evaporation is performed to obtain the target compound myrtenic acid in oil form; The molar ratio of the myrtenal, potassium dihydrogen phosphate, hydrogen peroxide, PEG-400, sodium chlorite and sodium sulfite is 1:0.25:1.1:0.14:1.3:0.

07.

4. The production method according to claim 2, characterized by: The synthesis of myrtenyl hydrazine comprises, Myrtenic acid is dissolved in anhydrous dichloromethane, and then DMAP and EDCI are added. Under ice bath condition, 85% hydrazine hydrate is added dropwise, after the addition is completed, the ice bath is removed, TLC detection is performed to determine whether the raw material is completely reacted, evaporation and concentration are performed to remove dichloromethane, ethyl acetate is added for extraction, the organic layers are combined, saturated brine is used for washing, anhydrous sodium sulfate is used for drying, and rotary evaporation is performed to obtain myrtenyl hydrazine crude product. Silica gel column chromatography separation and purification are performed, and the target compound myrtenyl hydrazine is obtained by purification with petroleum ether / ethyl acetate in a volume ratio of 10:1 to 3:

1. The molar ratio of the myrtenic acid, DMAP, EDCI and hydrazine hydrate is 1:0.1:1.2:

2.

5. The production method according to claim 2, wherein: The synthesis of myrtenyl-1,3,4-oxadiazole methyl ester comprises, The myrtenyl hydrazide is dissolved in phosphorus oxychloride, and oxalyl chloride methyl ester is added drop by drop under ice bath, after completion of addition, the reaction is carried out at 85℃ for 2 to 3 hours, the reaction solution is poured into ice water and stirred, ethyl acetate is added for extraction, the organic layers are combined, washed with saturated sodium bicarbonate, dried with anhydrous sodium sulfate, and concentrated by rotary evaporation to obtain the crude myrtenyl-1,3,4-oxadiazole methyl ester, which is purified by column chromatography on 200-300 mesh silica gel, and purified by using petroleum ether / ethyl acetate with a volume ratio of 200:1 to 50:1 to obtain the target compound myrtenyl-1,3,4-oxadiazole methyl ester; The myrtenyl hydrazide and the oxalyl chloride methyl ester are in a molar ratio of 1:1.

5.

6. The production method according to claim 2, wherein: The synthesis of the myrtenyl-1,3,4-oxadiazole methyl hydrazine comprises, The myrtenyl-1,3,4-oxadiazole methyl ester is dissolved in anhydrous DMF in a pressure tube, substituted phenylhydrazine is added, the temperature is raised to 100℃, and the reaction is stopped after 48 hours, then the reaction solution is removed, ethyl acetate is added for extraction, the organic layers are combined, washed with saturated brine, dried with anhydrous sodium sulfate, and concentrated by rotary evaporation to obtain the substituted myrtenyl-1,3,4-oxadiazole methyl hydrazine, which is purified by column chromatography on 200-300 mesh silica gel, and purified by using petroleum ether / ethyl acetate with a volume ratio of 200:1 to 20:1 to obtain the target compound substituted myrtenyl-1,3,4-oxadiazole methyl hydrazine; The myrtenyl-1,3,4-oxadiazole methyl ester and the substituted phenylhydrazine are in a molar ratio of 1:2.

5.

7. The production method according to any one of claims 2 to 6, characterized by: The substituted phenylhydrazine comprises phenylhydrazine, 4-fluorophenylhydrazine, 4-chlorophenylhydrazine, 4-bromophenylhydrazine, 4-iodophenylhydrazine, 4-methylphenylhydrazine, 2-methylphenylhydrazine, 2-fluorophenylhydrazine, 3-fluorophenylhydrazine, 2-chlorophenylhydrazine, 3-chlorophenylhydrazine, 2-bromophenylhydrazine, 3-bromophenylhydrazine, and 4-methoxyphenylhydrazine.

8. The myrtenyl-1,3,4-oxadiazole methyl hydrazine compound of claim 1 is used for preventing and treating plant fungi in agriculture or forestry.

9. Use according to claim 8, wherein: The plant fungi comprise Botryosphaeria dothidea, Sclerotinia sclerotiorum, Botrytis cinerea, Phytophthora infestans, and Phytophthora capsici. The plant fungi comprise Botryosphaeria dothidea, Sclerotinia sclerotiorum, Botrytis cinerea, Phytophthora infestans, and Phytophthora capsici.

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